American Journal of Epidemiology - Advance Access

Impact of New Biomarkers of Myocardial Damage on Trends in Myocardial Infarction Hospital Admission Rates from Population-based Administrative Data

Sanfilippo, F. M., Hobbs, M. S. T., Knuiman, M. W., Hung, J. — 2008-05-08

Use of troponin testing in the diagnosis of myocardial infarction substantially increases the number of cases diagnosed as myocardial infarction among suspected cases in comparison with previous criteria. However, the impact of troponin testing on rates reported in national statistics that use routinely collected hospital morbidity data is uncertain. The authors developed Poisson regression models to estimate the effect of troponin testing on long-term trends in hospital admission rates in Perth, Western Australia, from 1980 to 2004. Troponin tests were used for 10.5% of patients with suspected myocardial infarction in 1996, rising rapidly to more than 90% of patients from 2001 onward. Fitted models that assumed a continuing linear decline estimated that 100% use of troponin testing in cases of suspected myocardial infarction would lead to an apparent increase in hospital admission rates of 42% (95% confidence interval (CI): 28, 56) in men and 21% (95% CI: 4, 41) in women as compared with rates that would be expected if previous linear trends had continued. Smaller effects of 30% (95% CI: 14, 48) in men and –2% (95% CI: –21, 20) in women were found in fitted models that assumed an underlying attenuating trend in the rates. Similarly constructed logistic regression trend models found no significant effect of troponin testing on trends in 28-day case-fatality.

Physical Activity during Adulthood and Adolescence in Relation to Renal Cell Cancer

2008-05-08

Evidence for a relation between physical activity and renal cell cancer has been inconsistent. The authors examined physical activity in relation to renal cell cancer in a large, prospective US cohort study of 482,386 participants (289,503 men and 192,883 women) aged 50–71 years at baseline (1995–1996). At baseline, participants reported their frequency of exercise of at least 20 minutes' duration, intensity of daily routine activity, and frequency of physical activity during adolescence. During 8.2 years of follow-up (through December 2003), 1,238 cases of renal cell cancer were ascertained. In multivariate Cox regression models adjusted for renal cell cancer risk factors, the authors observed that current exercise, routine physical activity, and activity during adolescence were associated with a reduced risk of renal cell cancer. The multivariate relative risks for the highest activity level as compared with the lowest were 0.77 (95% confidence interval (CI): 0.64, 0.92; p_trend = 0.10) for current exercise, 0.84 (95% CI: 0.57, 1.22; p_trend = 0.03) for routine physical activity, and 0.82 (95% CI: 0.68, 1.00; p_trend = 0.05) for activity during adolescence. The authors conclude that increased physical activity, including activity during adolescence, is associated with reduced risk of renal cell cancer.

Air Pollution, Asthma Attacks, and Socioeconomic Deprivation: A Small-Area Case-Crossover Study

2008-05-07

With few exceptions, studies of short-term health effects of air pollution use pollutant concentrations that are averaged citywide as exposure indicators. They are thus prone to exposure misclassification and consequently to bias. Measurement of the relations between air pollution and health, generally and in specific populations, could be improved by employing more geographically precise exposure estimates. The authors investigated short-term relations between ambient air pollution estimated in small geographic areas (French census blocks) and asthma attacks in Strasbourg, France, in 2000–2005—in the general population and in populations with contrasting levels of socioeconomic deprivation. Emergency health-care networks provided data on 4,683 telephone calls made for asthma attacks. Deprivation was estimated using a block-level index constructed from census data. Hourly concentrations of particulate matter less than 10 µm in aerodynamic diameter (PM₁₀), sulfur dioxide, nitrogen dioxide, and ozone were modeled by block with ADMS-Urban software. Adjusted case-crossover analyses showed that asthma calls were positively but not significantly associated with PM₁₀ (for a 10-µg x m^–3 increase, odds ratio (OR) = 1.035, 95% confidence interval (CI): 0.997, 1.075), sulfur dioxide (OR = 1.056, 95% CI: 0.979, 1.139), and nitrogen dioxide (OR = 1.025, 95% CI: 0.990, 1.062). No association was observed for ozone (OR = 0.998, 95% CI: 0.965, 1.032). Socioeconomic deprivation had no significant influence on these relations.

Fetal Growth Indicators and Perfluorinated Chemicals: A Study in the Danish National Birth Cohort

Fei, C., McLaughlin, J. K., Tarone, R. E., Olsen, J. — 2008-05-05

Perfluorooctanoate (PFOA) and perfluorooctanesulfonate (PFOS) are widespread persistent organic pollutants that have been associated with reduced birth weight at doses expected in many pregnant populations. The authors randomly selected 1,400 pregnant women and their newborns from the Danish National Birth Cohort (1996–2002) to investigate whether these compounds reduce organ growth. PFOS and PFOA were measured in maternal blood samples taken early in pregnancy. Placental weight, birth length, and head and abdominal circumferences were measured shortly after birth by trained midwives or nurses. Maternal PFOA levels in early pregnancy were associated with smaller abdominal circumference and birth length. For each ng/ml increase in PFOA, birth length decreased by 0.069 cm (95% confidence interval: 0.024, 0.113) and abdominal circumference decreased by 0.059 cm (95% confidence interval: 0.012, 0.106). An inverse association was also observed between PFOA and placental weight and head circumference, and a positive association was observed with newborn ponderal index, but none of these associations was statistically significant. Maternal PFOS levels were not associated with any of the five fetal growth indicators. These findings suggest that fetal exposure to PFOA but not PFOS during organ development may affect the growth of organs and the skeleton.

Invited Commentary: Postmenopausal Unopposed Estrogen and Breast Cancer Risk in the Women's Health Initiative--Before and Beyond

Linet, M. S. — 2008-05-05

Three large clinical trials provoked major debate when hormone replacement therapy (HRT) did not reduce coronary heart disease in postmenopausal women as expected from observational epidemiologic studies. Less discussion has ensued about breast cancer or other adverse events. In this issue of the Journal, investigators from the Women's Health Initiative (WHI) compare breast cancer findings from the randomized trial of unopposed estrogen with those from the large WHI observational study. This commentary briefly summarizes historical highlights of menopausal hormone use; risk-versus-benefit evaluations; scientific, clinical, and policy influences immediately before and during the WHI trial; breast cancer incidence trends; and the posttrial response in US clinical practice. Factors complicating interpretation of the results include differences in breast cancer risk profiles between women in the trial and those in the observational study cohort as well as heterogeneity in the definitions of menopause and prior use of HRT as applied by the WHI investigators to the two populations. Because millions of women use HRT, it is important to consider how the WHI and other research investigations might contribute to reducing gaps in understanding the relation between HRT and breast cancer risk.

Obesity Subtypes and Risk of Spontaneous versus Medically Indicated Preterm Births in Singletons and Twins

Salihu, H. M., Lynch, O., Alio, A. P., Liu, J. — 2008-05-01

Using data from the Missouri maternally linked files (1989–1997), the authors examined the association among maternal obesity, obesity subtypes, and spontaneous and medically indicated preterm (<37 weeks) and very preterm (<33 weeks) births in singletons and twins. Adjusted odds ratios were obtained with correction for intracluster correlation. The prevalence of obesity increased by 77% over the study period (p_trend < 0.001). Obese mothers had a lower risk for spontaneous preterm birth, and this was more pronounced among twins (odds ratio = 0.68, 95% confidence interval: 0.62, 0.75) than singletons (odds ratio = 0.84, 95% confidence interval: 0.82, 0.87). However, this association was present only among obese women who gained less than 0.69 kg/week for singletons and between 0.23 and 0.69 kg/week for twins. By contrast, obese mothers with singleton gestation had about 50% greater odds of medically indicated preterm (odds ratio = 1.46, 95% confidence interval: 1.39, 1.54) and very preterm (odds ratio = 1.49, 95% confidence interval: 1.34, 1.65) births, and the risk increases with ascending severity of obesity (p_trend < 0.01). For extreme obesity, the risk of medically indicated preterm and very preterm births was almost double that for nonobese women. Similar findings were observed in twins. These data suggest that obesity increases the risk for medically indicated but not spontaneous preterm birth in both singletons and twins.

Risk of Breast Cancer and Gynecologic Cancers in a Large Population of Nearly 50,000 Infertile Danish Women

Jensen, A., Sharif, H., Olsen, J. H., Kjaer, S. K. — 2008-04-29

Infertility is considered to influence the risk of breast cancer and gynecologic cancers. To assess this association, the authors used data from a large cohort of 54,362 women with a diagnosis of infertility who were referred to Danish fertility clinics between 1963 and 1998. Through 2003, 1,975 cancers were identified by linkage to the Danish Cancer Registry. Cancer risk was assessed through standardized incidence ratios (SIRs) and corresponding 95% confidence intervals, using general and parity-specific cancer incidence rates in the general population of Denmark as a reference. After adjustment for parity status, significantly increased SIRs were observed for breast (SIR = 1.08, 95% confidence interval: 1.01, 1.16) and ovarian (SIR = 1.46, 95% confidence interval: 1.24, 1.71) cancer. The risk of breast cancer increased with follow-up time. Similar risk patterns were observed for the different histologic types of breast cancer and all nonmucinous types of ovarian cancer, whereas the risk of mucinous ovarian cancers seemed not to be increased. These data thus suggest higher risks of breast and ovarian cancer among infertile women. However, since these results could not distinguish the effects of underlying infertility from the effects of fertility treatment, additional studies are needed to disentangle the effects of these two factors.

Conjugated Equine Estrogens and Breast Cancer Risk in the Women's Health Initiative Clinical Trial and Observational Study

2008-04-29

The Women's Health Initiative randomized controlled trial found a trend (p = 0.09) toward a lower breast cancer risk among women assigned to daily 0.625-mg conjugated equine estrogens (CEEs) compared with placebo, in contrast to an observational literature that mostly reports a moderate increase in risk with estrogen-alone preparations. In 1993–2004 at 40 US clinical centers, breast cancer hazard ratio estimates for this CEE regimen were compared between the Women's Health Initiative clinical trial and observational study toward understanding this apparent discrepancy and refining hazard ratio estimates. After control for prior use of postmenopausal hormone therapy and for confounding factors, CEE hazard ratio estimates were higher from the observational study compared with the clinical trial by 43% (p = 0.12). However, after additional control for time from menopause to first use of postmenopausal hormone therapy, the hazard ratios agreed closely between the two cohorts (p = 0.82). For women who begin use soon after menopause, combined analyses of clinical trial and observational study data do not provide clear evidence of either an overall reduction or an increase in breast cancer risk with CEEs, although hazard ratios appeared to be relatively higher among women having certain breast cancer risk factors or a low body mass index.

Maternal Asthma Medication Use and the Risk of Gastroschisis

2008-04-23

The objective of this study was to examine the association between maternal asthma medication use during the periconceptional period and the risk of gastroschisis. In this case-control study, the authors used data on deliveries enrolled in the National Birth Defects Prevention Study (1997–2002) from eight collaborating centers. The cases included 381 infants with isolated gastroschisis, and the controls were 4,121 liveborn infants without malformations. The asthma medications used during the periconceptional period (1 month prepregnancy through the third pregnancy month) were divided into two groups, antiinflammatory and bronchodilator, and analyzed separately. Users of multiple asthma medications during the periconceptional period were also examined. Logistic regression was used to estimate odds ratios and 95% confidence intervals while controlling for maternal age, race/ethnicity, education, smoking, folic acid/vitamin use, and other vasoactive medications. Maternal bronchodilator use showed an elevated statistically significant risk of gastroschisis (adjusted odds ratio = 2.06, 95% confidence interval: 1.19, 3.59). No significant association was found between maternal use of asthma antiinflammatory medications and gastroschisis. Because information on maternal asthma status/severity was not available, the effects of disease on the risk of gastroschisis cannot be ruled out. Additional research is needed in determining whether a real risk exists and for guiding asthma treatment.

Psychiatric Diagnoses in Historic and Contemporary Military Cohorts: Combat Deployment and the Healthy Warrior Effect

Larson, G. E., Highfill-McRoy, R. M., Booth-Kewley, S. — 2008-04-23

Research studies have identified heightened psychiatric problems among veterans of Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF). However, these studies have not compared incidence rates of psychiatric disorders across robust cohorts, nor have they documented psychiatric problems prior to combat exposure. The authors' objectives in this study were to determine incidence rates of diagnosed mental disorders in a cohort of Marines deployed to combat during OIF or OEF in 2001–2005 and to compare these with mental disorder rates in two historical and two contemporary military control groups. After exclusion of persons who had been deployed to a combat zone with a preexisting psychiatric diagnosis, the cumulative rate of post-OIF/-OEF mental disorders was 6.4%. All psychiatric conditions except post-traumatic stress disorder occurred at a lower rate in combat-deployed personnel than in personnel who were not deployed to a combat zone. The findings suggest that psychiatric disorders in Marines are diagnosed most frequently during the initial months of recruit training rather than after combat deployment. The disproportionate loss of psychologically unfit personnel early in training creates a "healthy warrior effect," because only those persons who have proven their resilience during training remain eligible for combat.

Familial Aggregation of Cryptorchidism--A Nationwide Cohort Study

2008-04-23

Although cryptorchidism is the most common birth defect in boys affecting 4–9 percent of newborns and 1–2 percent of boys 1 year of age, the etiology remains largely unknown. The authors investigated the contribution of genetic and environmental factors to familial aggregation of cryptorchidism. Using Danish health registers, they identified 25,395 boys diagnosed with cryptorchidism in a cohort of 1,022,713 boys born in 1977–2005. Using binomial log-linear regression, they estimated recurrence risk ratios (RRRs) of cryptorchidism for male twin pairs and first-, second-, and third-degree relatives of a cryptorchidism case. The RRR in same-sex twins was 10.1 (95% confidence interval (CI): 7.78, 13.1). The RRR among first-degree relatives was significantly higher among brothers (RRR = 3.52, 95% CI: 3.26, 3.79) than for offspring of a cryptorchidism case (RRR = 2.31, 95% CI: 2.09, 2.54). The RRR was also found to be significantly higher in maternal (RRR = 2.12, 95% CI: 1.74, 2.60) than paternal (RRR = 1.28, 95% CI: 1.01, 1.61) half brothers. In conclusion, inherited factors were found to have a moderate influence on the risk of cryptorchidism. The data are compatible with the hypothesis that maternal factors operating in utero are important for the risk of cryptorchidism.

Invited Commentary: How Healthy is the "Healthy Warrior"?

Toomey, R. — 2008-04-22

In this issue of the Journal, Larson et al. (Am J Epidemiol 2008;000:000–00) report incidence rates of 11.8% for any mental disorder and 1.6% for post-traumatic stress disorder among US Marines deployed during Operation Iraqi Freedom and Operation Enduring Freedom. Various methodological reasons can help explain why these rates are lower than those found in previous wars. One primary reason is varying methods of diagnosis. Other reasons include differences in percentages of active-duty personnel, windows of observation, and methods of calculating rates. In addition, comorbidity for some mental disorders and specific risks for developing certain disorders complicate interpretation of rates. Nevertheless, Larson et al. document evidence for the "healthy warrior" effect—namely that deployed Marines have fewer mental disorders than nondeployed Navy and Marine Corps personnel, with the exception of stress disorders. Suggestions are made for directions of future research into this effect.

Are Patients with Skin Cancer at Lower Risk of Developing Colorectal or Breast Cancer?

2008-04-17

Ultraviolet exposure may reduce the risk of colorectal and breast cancer as the result of rising vitamin D levels. Because skin cancer is positively related to sun exposure, the authors hypothesized a lower incidence of breast and colorectal cancer after skin cancer diagnosis. They analyzed the incidence of colorectal and breast cancer diagnosed from 1972 to 2002 among 26,916 Netherlands skin cancer patients (4,089 squamous cell carcinoma (SCC), 19,319 basal cell carcinoma (BCC), and 3,508 cutaneous malignant melanoma (CMM)). Standardized incidence ratios were calculated. A markedly decreased risk of colorectal cancer was found for subgroups supposedly associated with the highest accumulated sun exposure: men (standardized incidence ratio (SIR) = 0.83, 95% confidence interval (CI): 0.71, 0.97); patients with SCC (SIR = 0.64, 95% CI: 0.43, 0.93); older patients at SCC diagnosis (SIR = 0.59, 95% CI: 0.37, 0.88); and patients with a SCC or BCC lesion on the head and neck area (SIR = 0.59, 95% CI: 0.36, 0.92 for SCC and SIR = 0.78, 95% CI: 0.63, 0.97 for BCC). Patients with CMM exhibited an increased risk of breast cancer, especially advanced breast cancer (SIR = 2.20, 95% CI: 1.10, 3.94) and older patients at CMM diagnosis (SIR = 1.87, 95% CI: 1.14, 2.89). Study results suggest a beneficial effect of continuous sun exposure against colorectal cancer. The higher risk of breast cancer among CMM patients may be related to socioeconomic class, both being more common in the affluent group.

Understanding Sequelae of Injury Mechanisms and Mild Traumatic Brain Injury Incurred during the Conflicts in Iraq and Afghanistan: Persistent Postconcussive Symptoms and Posttraumatic Stress Disorder

Schneiderman, A. I., Braver, E. R., Kang, H. K. — 2008-04-17

A cross-sectional study of military personnel following deployment to conflicts in Iraq or Afghanistan ascertained histories of combat theater injury mechanisms and mild traumatic brain injury (TBI) and current prevalence of posttraumatic stress disorder (PTSD) and postconcussive symptoms. Associations among injuries, PTSD, and postconcussive symptoms were explored. In February 2005, a postal survey was sent to Iraq/Afghanistan veterans who had left combat theaters by September 2004 and lived in Maryland; Washington, DC; northern Virginia; and eastern West Virginia. Immediate neurologic symptoms postinjury were used to identify mild TBI. Adjusted prevalence ratios and 95% confidence intervals were computed by using Poisson regression. About 12% of 2,235 respondents reported a history consistent with mild TBI, and 11% screened positive for PTSD. Mild TBI history was common among veterans injured by bullets/shrapnel, blasts, motor vehicle crashes, air/water transport, and falls. Factors associated with PTSD included reporting multiple injury mechanisms (prevalence ratio = 3.71 for three or more mechanisms, 95% confidence interval: 2.23, 6.19) and combat mild TBI (prevalence ratio = 2.37, 95% confidence interval: 1.72, 3.28). The strongest factor associated with postconcussive symptoms was PTSD, even after overlapping symptoms were removed from the PTSD score (prevalence ratio = 3.79, 95% confidence interval: 2.57, 5.59).

Association of Birth Outcomes and Maternal, School, and Neighborhood Characteristics with Subsequent Numeracy Achievement

Malacova, E., Li, J., Blair, E., Leonard, H., Klerk, N. d., Stanley, F. — 2008-04-15

This study investigated the relation between birth characteristics and numeracy attainment at age 8 years. Using a multilevel approach, the authors analyzed all non-Aboriginal singletons born in Western Australia who attended government schools and participated in a Western Australia–wide numeracy test in grade 3 between 1999 and 2005. Appropriateness of intrauterine growth was expressed as the proportion of optimal growth parameters for gestational duration, infant sex, and maternal height and parity, which was derived from a total population of births without risk factors for growth restriction. After the authors controlled for sociodemographic factors, term birth and proportion of optimal head circumference at birth were associated with higher numeracy scores. Increasing proportion of optimal birth length and being firstborn were associated with relatively higher numeracy scores among children born to mothers residing in the most educationally deprived area. The relative advantage of being born first was also higher for children born to single mothers. In contrast, higher Apgar scores and greater proportion of optimal birth weight were associated with a lower relative advantage for children born to single mothers. In summary, term birth and increased growth in head circumference and length are key birth characteristics associated with higher numeracy scores, especially among disadvantaged children.

Waist Circumference and Mortality

2008-04-15

The authors examined the association between waist circumference and mortality among 154,776 men and 90,757 women aged 51–72 years at baseline (1996–1997) in the NIH-AARP Diet and Health Study. Additionally, the combined effects of waist circumference and body mass index (BMI; weight (kg)/height (m)²) were examined. All-cause mortality was assessed over 9 years of follow-up (1996–2005). After adjustment for BMI and other covariates, a large waist circumference (fifth quintile vs. second) was associated with an approximately 25% increased mortality risk (men: hazard ratio (HR) = 1.22, 95% confidence interval (CI): 1.15, 1.29; women: HR = 1.28, 95% CI: 1.16, 1.41). The waist circumference-mortality association was found in persons with and without prevalent disease, in smokers and nonsmokers, and across different racial/ethnic groups (non-Hispanic Whites, non-Hispanic Blacks, Hispanics, and Asians). Compared with subjects with a combination of normal BMI (18.5–<25) and normal waist circumference, those in the normal-BMI group with a large waist circumference (men: ≥102 cm; women: ≥88 cm) had an approximately 20% higher mortality risk (men: HR = 1.23, 95% CI: 1.08, 1.39; women: HR = 1.22, 95% CI: 1.09, 1.36). The finding that persons with a normal BMI but a large waist circumference had a higher mortality risk in this study suggests that increased waist circumference should be considered a risk factor for mortality, in addition to BMI.

A Regression Approach for Estimating Multiday Adverse Health Effects of PM10 When Daily PM10 Data Are Unavailable

Martin, M. A., Roberts, S. — 2008-04-15

The authors propose a regression-based approach for obtaining multiday estimates of the adverse health effects of ambient particulate matter less than 10 µm in diameter (PM₁₀) when daily PM₁₀ time-series data are unavailable. This situation is common in the United States, because most US cities take PM₁₀ measurements every 6 days. Current evidence suggests that adverse effects of PM₁₀ are not concentrated on a single day but rather are spread out over multiple days, so the unavailability of daily PM₁₀ data presents a problem for the estimation of these effects. The proposed model estimates weights that are used to construct a linear combination of single-lag PM₁₀ effect estimates obtained from the available PM₁₀ data. It is shown that this new approach provides estimates of the effect of PM₁₀ on mortality that have less bias and mean squared error than currently available methods. Application of this method to the US cities contained in the National Morbidity, Mortality, and Air Pollution Study database produces an estimated national average effect of PM₁₀ on nonaccidental mortality in persons over age 65 years, corresponding to a 0.32% increase per 10-µg/m³ increment in PM₁₀. The estimated effects for cardiorespiratory mortality and other mortality are 0.34% and 0.22%, respectively.

Association of Site-specific and Participant-specific Factors with Retention of Children in a Long-term Pediatric HIV Cohort Study

2008-04-15

Minimizing loss to follow-up (LTFU) in long-term cohort studies is essential for reducing bias and maintaining statistical stability. However, factors associated with attrition of children in observational studies have received little attention. The authors used survival analysis methods to evaluate the association of participant and site characteristics with time to LTFU in a multicenter cohort study conducted in the United States of 2,693 human immunodeficiency virus (HIV)-infected and 1,370 HIV-exposed-but-uninfected children enrolled in 2000–2004. As of 2004, 91% of HIV-infected and 86% of uninfected children had been retained in the study. Among the HIV infected, factors associated with higher risk of LTFU included site prohibition of participant compensation, low caregiver educational level, age >15 years, and higher viral load, whereas death of a family member was associated with better retention. Among uninfected children, sites accruing low numbers of subjects, social worker responsible for retention, young age (1–2 years), and birth abnormalities were associated with higher risk of LTFU. Occurrences of certain stressful life events, such as a death in the family or financial instability, were associated with higher retention, but risk of LTFU increased when children started school or mothers began employment. Although participant characteristics are difficult to modify, the authors identified several potentially modifiable site practices that could be targeted to improve retention.

Insulin-like Growth Factor 1, Insulin-like Growth Factor-Binding Protein 3, and Testicular Germ-Cell Tumor Risk

2008-04-11

Studies have consistently shown that taller men are at increased risk of testicular germ-cell tumors. Thus, it is plausible that factors associated with height may also influence risk of these tumors. The authors examined associations between testicular germ-cell tumor risk and circulating concentrations of insulin-like growth factor 1 (IGF-1) and insulin-like growth factor-binding protein 3 (IGFBP-3) among 517 cases and 790 controls from the US Servicemen's Testicular Tumor Environmental and Endocrine Determinants (STEED) Study (2002–2005). Odds ratios and 95% confidence intervals were estimated using logistic regression models, adjusting for age, race/ethnicity, height, and body mass index. All tests of significance were two-sided. Overall, there were no associations between IGF-1 or IGFBP-3 concentrations and risk of testicular germ-cell tumors (p > 0.05). However, when cases were separated by histologic type, there was a suggestion of a reduction in seminoma risk associated with the highest concentrations of IGF-1 as compared with the lowest concentrations (odds ratio = 0.66, 95% confidence interval: 0.40, 1.09). Although there were no overall associations with insulin-like growth factor, contrary to expectation, there was a suggestion that IGF-1 concentrations may be inversely associated with risk of seminoma.

Parental Subfecundity and Risk of Decreased Semen Quality in the Male Offspring: A Follow-up Study

Ramlau-Hansen, C. H., Thulstrup, A. M., Olsen, J., Bonde, J. P. — 2008-04-11

A few studies have found poor semen quality in sons whose mothers have received fertility treatment, but it is unknown whether the poor semen quality is related to the infertility treatment or to infertility per se, for example, whether it is caused by hereditable factors. Using data from a population-based, Danish follow-up study conducted in 2005–2006, the authors of the present study examined whether sons of subfertile couples who had not received fertility treatment had poorer semen quality than sons of fertile couples. Among the 311 participants, an inverse association between parental waiting time to pregnancy and both semen volume and total sperm count was observed (p trend = 0.04 and p trend = 0.046, respectively). Semen volume in sons of subfertile parents (pregnant after ≥1 years) was 19% lower in comparison with that in sons of parents whose waiting time to pregnancy was 0–6 months (p = 0.02). Additionally, sperm concentration and percentage of morphologically normal sperm were, respectively, 22% (p = 0.15) and 23% (p = 0.13) lower in sons of subfertile parents. Results suggest a small-to-moderate effect of parental subfecundity on semen quality in sons, comparable with the hypothesis that low fecundity has at least partly hereditable causes.

Does Temperature Modify the Association between Air Pollution and Mortality? A Multicity Case-Crossover Analysis in Italy

Stafoggia, M., Schwartz, J., Forastiere, F., Perucci, C. A., the SISTI Group — 2008-04-11

Adverse health effects of particulate matter <10 µm in aerodynamic diameter (PM₁₀) and high temperatures are well known, but the extent of their interaction on mortality is less clear. This paper describes effect modification of temperature in the PM₁₀–mortality association and tests the hypothesis that higher PM₁₀ effects in summer are due to enhanced exposure to particles. All deaths of residents of nine Italian cities between 1997 and 2004 were selected. The case-crossover approach was adopted to estimate the effect of PM₁₀ on mortality by season and temperature level. Three strata of temperature corresponding to low, medium, and high "ventilation" were identified, and the interaction between PM₁₀ and temperature within each stratum was examined. Season and temperature levels strongly modified the PM₁₀–mortality association: for a 10-µg/m³ variation in PM₁₀, a 2.54% increase in risk of death in summer (95% confidence interval: 1.31, 3.78) compared with 0.20% (95% confidence interval: –0.08, 0.49) in winter. Analysis of the interaction between PM₁₀ and temperature within temperature strata resulted in positive but, in most cases, nonstatistically significant coefficients. The authors found much higher PM₁₀ effects on mortality during warmer days. The hypothesis that such an effect is attributable to enhanced exposure to particles in summer could not be rejected.

Alcohol Drinking and Colorectal Cancer in Japanese: A Pooled Analysis of Results from Five Cohort Studies

2008-04-11

Colorectal cancer is an alcohol-related malignancy; however, the association appears to be stronger among Asian populations with a relatively high prevalence of the slow-metabolizing aldehyde dehydrogenase variant. To examine the association between alcohol consumption and colorectal cancer in Japanese, the authors analyzed original data from five cohort studies that measured alcohol intake using validated questionnaires at baseline. Hazard ratios were calculated in the individual studies, with adjustment for a common set of variables, and then combined using a random-effects model. During 2,231,010 person-years of follow-up (ranging variously from 1988 to 2004), 2,802 colorectal cancer cases were identified. In men, multivariate-adjusted pooled hazard ratios for alcohol intakes of 23–45.9 g/day, 46–68.9 g/day, 69–91.9 g/day, and ≥92 g/day, compared with nondrinking, were 1.42 (95% confidence interval (CI): 1.21, 1.66), 1.95 (95% CI: 1.53, 2.49), 2.15 (95% CI: 1.74, 2.64), and 2.96 (95% CI: 2.27, 3.86), respectively (p for trend < 0.001). The association was evident for both the colon and the rectum. A significant positive association was also observed in women. One fourth of colorectal cancer cases in men were attributable to an alcohol intake of ≥23 g/day. An alcohol-colorectal cancer association seems to be more apparent in Japanese than in Western populations. Whether this difference can be ascribed to genetic or environmental factors needs to be clarified.

Personal Use of Hair Dye and the Risk of Certain Subtypes of Non-Hodgkin Lymphoma

2008-04-11

Personal use of hair dye has been inconsistently linked to risk of non-Hodgkin lymphoma (NHL), perhaps because of small samples or a lack of detailed information on personal hair-dye use in previous studies. This study included 4,461 NHL cases and 5,799 controls from the International Lymphoma Epidemiology Consortium 1988–2003. Increased risk of NHL (odds ratio (OR) = 1.3, 95% confidence interval (CI): 1.1, 1.4) associated with hair-dye use was observed among women who began using hair dye before 1980. Analyses by NHL subtype showed increased risk for follicular lymphoma (FL) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) but not for other NHL subtypes. The increased risks of FL (OR = 1.4, 95% CI: 1.1, 1.9) and CLL/SLL (OR = 1.5, 95% CI: 1.1, 2.0) were mainly observed among women who started using hair dyes before 1980. For women who began using hair dye in 1980 or afterward, increased FL risk was limited to users of dark-colored dyes (OR = 1.5, 95% CI: 1.1, 2.0). These results indicate that personal hair-dye use may play a role in risks of FL and CLL/SLL in women who started use before 1980 and that increased risk of FL among women who started use during or after 1980 cannot be excluded.

Geographic Prevalence and Multilevel Determination of Community-level Factors Associated with Herpes Simplex Virus Type 2 Infection in Chennai, India

2008-04-09

Herpes simplex virus type 2 (HSV-2) is one of the most prevalent sexually transmitted infections, and it increases the risk of transmission of human immunodeficiency virus type 1 at least twofold. Individual-level factors are insufficient to explain geographic and population variation in HSV-2, suggesting the need to identify ecologic factors. The authors sought to determine the geographic prevalence and community-level factors associated with HSV-2 after controlling for individual-level factors among slums in Chennai, India. From March to June 2001, participants aged 18–40 years voluntarily completed a survey and were tested for HSV-2. Community characteristics were assessed through interviews with key informants and other secondary data sources. Multilevel nonlinear analysis was conducted. Eighty-five percent of eligible persons completed the survey; of these, 98% underwent HSV-2 testing, producing a final sample of 1,275. Participants were of Tamil ethnicity, were predominantly female and married, and were on average 30 years old. Fifteen percent were infected with HSV-2, and there was significant variation in HSV-2 prevalence among communities. After controlling for individual-level factors, the authors identified community-level factors, including socioeconomic status and the presence of injection drug users, that were independently associated with HSV-2 and explained 11% of the variance in prevalence. Future studies are needed to test mechanisms through which these community-level factors may be operating.

Diabetic Control and Risk of Tuberculosis: A Cohort Study

2008-04-08

Diabetes mellitus is associated with tuberculosis. A cohort of 42,116 clients aged 65 years or more, enrolled at 18 Elderly Health Service centers in Hong Kong in 2000, were followed up prospectively through the territory-wide tuberculosis registry for development of tuberculosis from 3 months after enrollment to December 31, 2005, by use of their identity card numbers as unique identifier. The effects of diabetes mellitus and diabetic control on tuberculosis risk were assessed with adjustment for sociodemographic and other background variables. Diabetes mellitus was associated with a modest increase in the risk of active, culture-confirmed, and pulmonary (with or without extrapulmonary involvement) but not extrapulmonary (with or without pulmonary involvement) tuberculosis, with adjusted hazard ratios of 1.77 (95% confidence interval: 1.41, 2.24), 1.91 (95% confidence interval: 1.45, 2.52), 1.89 (95% confidence interval: 1.48, 2.42), and 1.00 (95% confidence interval: 0.54, 1.86), respectively. Diabetic subjects with hemoglobin A1c <7% at enrollment were not at increased risk. Among diabetic subjects, higher risks of active, culture-confirmed, and pulmonary but not extrapulmonary tuberculosis were observed with baseline hemoglobin A1c ≥7% (vs. <7%), with adjusted hazard ratios of 3.11 (95% confidence interval: 1.63, 5.92), 3.08 (95% confidence interval: 1.44, 6.57), 3.63 (95% confidence interval: 1.79, 7.33), and 0.77 (95% confidence interval: 0.18, 3.35), respectively.

Toenail Nicotine Levels as Predictors of Coronary Heart Disease among Women

Al-Delaimy, W. K., Stampfer, M. J., Manson, J. E., Willett, W. C. — 2008-04-07

The authors assess the ability of toenail nicotine levels as a biomarker to predict incident coronary heart disease (CHD). A nested case-control study was carried out among 62,641 women aged 36–61 years in the Nurses' Health Study cohort who provided toenail clippings in 1982. Between 1984 and 1998, 905 incident CHD cases were diagnosed and matched with two controls by age and date of toenail collection. Using multivariate logistic regression analyses, the authors found a statistically significant dose-response association between increasing toenail nicotine levels and risk of CHD (p_trend < 0.0001); women in the highest quintile had a relative risk of 3.44 (95% confidence interval (CI): 2.56, 4.62) compared with women in the lowest quintile. With each increase in the log-transformed unit of continuous toenail nicotine levels, there was a 42% increase in the risk of CHD (relative risk = 1.42, 95% CI: 1.33, 1.52). The association remained significant when the number of cigarettes smoked and passive smoking were included as covariates (relative risk = 1.12, 95% CI: 1.01, 1.24). In conclusion, toenail nicotine levels are predictive of CHD among women independent of other risk factors and remained significant even after adjustment for history of cigarette smoking.

The Shanghai Women's Asthma and Allergy Study: Objectives, Design, and Recruitment Results

2008-04-07

The Shanghai Women's Asthma and Allergy Study is the first population-based incidence study designed to assess the associations of dietary antioxidant intake and measures of oxidative stress and antioxidant enzyme activity with development of adult-onset asthma and allergic rhinitis. A total of 65,732 participants in the Shanghai Women's Health Study, an ongoing cohort study in seven districts of Shanghai, People's Republic of China, were recruited to the Shanghai Women's Asthma and Allergy Study from 2003 to 2007. Dietary intake was assessed in the parent study by using a validated and quantitative food frequency questionnaire at baseline recruitment and at the first biennial follow-up survey. Blood and urine samples were collected to measure baseline oxidative stress, antioxidant enzyme activity, and nutrient levels at the baseline survey. Incident asthma and allergic rhinitis were assessed by using a modification of the International Study of Asthma and Allergies in Childhood questionnaire during the biennial in-person survey of the Shanghai Women's Health Study. Diagnosis of asthma was confirmed by either methacholine challenge testing or test of reversibility to beta-agonists. Dietary antioxidant intake, plasma antioxidants, antioxidant enzymes, and urinary isoprostanes, a marker of oxidative stress, were measured prior to disease onset. This paper describes the study objectives, design, population demographics, and recruitment results.

Analgesic Drug Use and Risk of Epithelial Ovarian Cancer

Hannibal, C. G., Rossing, M. A., Wicklund, K. G., Cushing-Haugen, K. L. — 2008-04-04

Analgesic use may reduce ovarian cancer risk, possibly through antiinflammatory or antigonadotropic effects. The authors conducted a population-based, case-control study in Washington State that included 812 women aged 35–74 years who were diagnosed with epithelial ovarian cancer between 2002 and 2005 and 1,313 controls. Use of analgesics, excluding use within the previous year, was assessed via in-person interviews. Logistic regression was used to calculate odds ratios and 95% confidence intervals. Overall, acetaminophen and aspirin were associated with weakly increased risks of ovarian cancer. These associations were stronger after more than 10 years of use (acetaminophen: odds ratio (OR) = 1.8, 95% confidence interval (CI): 1.3, 2.6; aspirin: OR = 1.6, 95% CI: 1.1, 2.2) and were present for indications of headache, menstrual pain, and other pain/injury. Reduced risk was observed among aspirin users who began regular use within the previous 5 years (OR = 0.6, 95% CI: 0.4, 1.0) or used this drug for prevention of heart disease (OR = 0.7, 95% CI: 0.5, 1.0). These results, in the context of prior findings, do not provide compelling evidence of a true increase in risk of ovarian cancer among women who use these drugs. However, they add to the weight of evidence that, in the aggregate, provides little support for the use of analgesic drugs as chemoprevention for this disease.

Association between Serum trans-Monounsaturated Fatty Acids and Breast Cancer Risk in the E3N-EPIC Study

2008-04-04

The authors assessed the association between serum phospholipid fatty acids as biomarkers of fatty acid intake and breast cancer risk among women in the E3N Study (1989–2002), the French component of the European Prospective Investigation into Cancer and Nutrition. During an average of 7 years of follow-up, 363 cases of incident invasive breast cancer were documented among 19,934 women who, at baseline (1995–1998), had completed a diet history questionnaire and provided serum samples. Controls were randomly matched to cases by age, menopausal status at blood collection, fasting status at blood collection, date, and collection center. Serum phospholipid fatty acid composition was assessed by gas chromatography. Adjusted odds ratios for risk of breast cancer with increasing levels of fatty acids were calculated using conditional logistic regression. An increased risk of breast cancer was associated with increasing levels of the trans-monounsaturated fatty acids palmitoleic acid and elaidic acid (highest quintile vs. lowest: odds ratio = 1.75, 95% confidence interval: 1.08, 2.83; p-trend = 0.018). cis-Monounsaturated fatty acids were unrelated to breast cancer risk. A high serum level of trans-monounsaturated fatty acids, presumably reflecting a high intake of industrially processed foods, is probably one factor contributing to increased risk of invasive breast cancer in women.

Trend of Increase in the Incidence of Acute Myocardial Infarction in a Japanese Population: Takashima AMI Registry, 1990-2001

2008-04-01

The incidence and mortality of acute myocardial infarction (AMI) remain low in Japan despite major dietary changes and worsening cardiovascular risk factors, a situation that should have resulted in a substantial increase in AMI rates (Japanese paradox). The current trend in the incidence of AMI was examined for the period 1990–2001 by use of data from the Takashima AMI Registry covering a stable population of approximately 55,000 in central Japan. AMI incidence rates (per 100,000 person-years) and 95% confidence intervals were calculated for 1990–1992, 1993–1995, 1996–1998, and 1999–2001. The incidence trend was determined by calculating the average annual change in percentage across the years. There were 352 (men: n = 224; women: n = 128) registered first-ever AMI cases during 1990–2001. The age-adjusted incidence rate of all AMI showed a gradual increase from 39.9 (95% confidence interval (CI): 29.8, 50.0) in 1990–1992 to 62.6 (95% CI: 51.5, 73.7) in 1999–2001. In men, the age-adjusted incidence rate increased from 66.5 (95% CI: 46.4, 86.6) in 1990–1992 to 100.7 (95% CI: 78.6, 122.7) in 1999–2001. In women, fluctuation was observed after an initial steep increase. The average annual incidence increased by 7.6% (95% CI: 3.5, 11.7) among men and by 8.3% (95% CI: 1.02, 15.6) among women. To the best of the authors' knowledge, this is the first study to report an increasing trend of AMI in a Japanese population.

Risk of Oral Clefts in Relation to Prepregnancy Weight Change and Interpregnancy Interval

Villamor, E., Sparen, P., Cnattingius, S. — 2008-03-28

Epidemiologic evidence regarding the influence of maternal obesity on the risk of oral clefts is inconsistent. It is unknown whether increases in maternal weight before pregnancy are related to the risk of these malformations. The authors conducted a population-based cohort study in Sweden among 220,328 women who had their first two pregnancies between 1992 and 2004. The risk of oral clefts during the second pregnancy was estimated in relation to maternal change in body mass index (BMI; weight (kg)/height (m)²) from the beginning of the first pregnancy to the beginning of the second pregnancy. Among women whose second-pregnancy BMI was ≥3 units higher than their first-pregnancy BMI, the adjusted risk of isolated cleft palate was 2.3 times higher (95% confidence interval: 1.4, 4.0) as compared with women whose BMI did not change substantially. BMI change was not related to the risk of cleft lip. Unexpectedly, the birth prevalence of isolated cleft palate per 1,000 livebirths increased linearly with the length of the interpregnancy interval, from 0.3 in women with intervals of <12 months to 0.9 in women with intervals of ≥48 months (adjusted p for trend = 0.002). High prepregnancy maternal weight gain and long interpregnancy intervals appear to be associated with increased risk of cleft palate.

Impact of Body Mass Index on Incident Hypertension and Diabetes in Chinese Asians, American Whites, and American Blacks: The People's Republic of China Study and the Atherosclerosis Risk in Communities Study

Stevens, J., Truesdale, K. P., Katz, E. G., Cai, J. — 2008-03-28

Researchers have hypothesized that the impact of body mass index on chronic disease may be greater in Asians than in Whites; however, most studies are cross-sectional and have no White comparison group. The authors compared the associations with body mass index in Chinese Asians (n = 5,980), American Whites (n = 10,776), and American Blacks (n = 3,582) using prospective data from the People's Republic of China Study (1983–1994) and the Atherosclerosis Risk in Communities Study (1987–1998). Slopes of risk differences over body mass index levels were compared among the three ethnic groups in adjusted analyses. The authors found larger associations with body mass index in Chinese Asians compared with American Whites and Blacks for hypertension (p < 0.05). The increase in the incidence of hypertension associated with a one-unit increase in body mass index over approximately 8 years of follow-up was 2.5, 1.7, and 1.8 percentage points for Chinese Asians, American Whites, and American Blacks, respectively. For diabetes, the estimates were 1.7, 1.1, and 1.6 percentage points for the same groups— higher in Chinese Asians than in American Whites (p < 0.05) but similar between Chinese Asians and American Blacks. Given the ethnic differences in associations, the results support advocacy of public health and medical actions toward obesity prevention and treatment in China.

Maternal Age, Exposure to Siblings, and Risk of Amyotrophic Lateral Sclerosis

Fang, F., Kamel, F., Sandler, D. P., Sparen, P., Ye, W. — 2008-03-25

Between 1987 and 2005, the authors conducted a nested case-control study based on the Swedish Multi-Generation Register to investigate whether early life exposures, namely, maternal age at delivery and exposure to siblings, are associated with an increased risk of amyotrophic lateral sclerosis (ALS). The study comprised 768 ALS cases and five controls per case matched by birth year and gender. Odds ratios and their corresponding 95% confidence intervals for ALS were estimated by conditional logistic regression modeling. Low maternal age (≤20 years) and high maternal age (≥41 years) were both associated with higher risk of ALS (odds ratio (OR) = 1.5, 95% confidence interval (CI): 1.1, 2.0 and OR = 1.7, 95% CI: 1.1, 2.4, respectively). The relative risk of ALS increased slightly with increasing number of younger siblings (OR = 1.1, 95% CI: 1.0, 1.1; p = 0.02). Children whose first younger sibling was born after the age of 6 years had the greatest relative risk (OR = 1.8, 95% CI: 1.2, 2.7). Exposure to older siblings was not associated with the risk of ALS. Although the strength of the observed associations was modest, these results provided further support for the theory that early life exposures might contribute to the disease pathogenesis.

Effects of Socioeconomic Position on Inflammatory and Hemostatic Markers: A Life-Course Analysis in the 1958 British Birth Cohort

Tabassum, F., Kumari, M., Rumley, A., Lowe, G., Power, C., Strachan, D. P. — 2008-03-25

The cumulative effects of socioeconomic position (SEP) on cardiovascular disease have been described, but the pathways are unclear. In this study, the authors examined the effects of life-course SEP on inflammatory and hemostatic markers: fibrinogen, C-reactive protein, von Willebrand factor antigen, and tissue plasminogen activator antigen. Data from the 1958 British birth cohort, including data on persons who underwent a biomedical follow-up in 2002–2004, were used. Social class was determined at three stages of respondents' lives: childhood (birth), early adulthood (age 23 years), and midlife (age 42 years). A cumulative indicator score of SEP was calculated that ranged from 0 (always in the highest social class) to 9 (always in the lowest social class). In men and women, associations were observed between cumulative indicator score and fibrinogen (p < 0.001), C-reactive protein (p < 0.001), von Willebrand factor antigen (p ≤ 0.05), and tissue plasminogen activator antigen (p < 0.001 only in women). The trends in fibrinogen and C-reactive protein remained after adjustment for body mass index, smoking, and physical activity. However, the trends became nonsignificant for von Willebrand factor antigen and tissue plasminogen activator antigen in women. Risk exposure related to SEP accumulates across the life course and contributes to raised levels of fibrinogen and C-reactive protein, while childhood SEP influences hemostatic markers more than does adult SEP.

Relation between Neighborhood Environments and Obesity in the Multi-Ethnic Study of Atherosclerosis

2008-03-25

This study investigated associations between neighborhood physical and social environments and body mass index in 2,865 participants of the Multi-Ethnic Study of Atherosclerosis (MESA) aged 45–84 years and residing in Maryland, New York, and North Carolina. Neighborhood (census tract) environments were measured in non-MESA participants residing in MESA neighborhoods (2000–2002). The neighborhood physical environment score combined measures of a better walking environment and greater availability of healthy foods. The neighborhood social environment score combined measures of greater aesthetic quality, safety, and social cohesion and less violent crime. Marginal maximum likelihood was used to estimate associations between neighborhood environments and body mass index (kg/m²) before and after adjustment for individual-level covariates. MESA residents of neighborhoods with better physical environments had lower body mass index (mean difference per standard deviation higher neighborhood measure = –2.38 (95% confidence interval (CI): –3.38, –1.38) kg/m² for women and –1.20 (95% CI: –1.84, –0.57) kg/m² for men), independent of age, race/ethnicity, education, and income. Attenuation of these associations after adjustment for diet and physical activity suggests a mediating role of these behaviors. In men, the mean body mass index was higher in areas with better social environments (mean difference = 0.52 (95% CI: 0.07, 0.97) kg/m²). Improvement in the neighborhood physical environment should be considered for its contribution to reducing obesity.

Are Racial Disparities in Preterm Birth Larger in Hypersegregated Areas?

Osypuk, T. L., Acevedo-Garcia, D. — 2008-03-25

The causes of the racial/ethnic disparity in preterm birth (PTB) remain largely unknown; traditional risk factors such as smoking and prenatal care fail to account for it. The authors examined whether living in metropolitan areas (MAs) with high levels of residential racial segregation along multiple dimensions (hypersegregation) was associated with higher rates of PTB or larger racial disparities in PTB and whether segregation modified the established race-age association in PTB. The authors merged 2000 natality data (n = 1,944,703) with US Census measures of Black-White hypersegregation. They executed two-level hierarchical logistic regression analyses among White and Black mothers in 237 MAs to estimate the odds of PTB by hypersegregation, race, and age, after controlling for covariates. In unadjusted and adjusted models, Black infants in hypersegregated MAs were more likely to be preterm than Black infants in nonhypersegregated MAs (p < 0.001). Black-White PTB disparities were larger in hypersegregated areas than in nonhypersegregated areas (p < 0.001), and the age-race association with PTB was modified by hypersegregation (p < 0.001). Living in a hypersegregated MA had a more pronounced association with PTB among older Black women, and racial disparities in PTB were larger in hypersegregated areas among older mothers (p < 0.001). Since over 40% of Black childbearing women live in hypersegregated areas, residential segregation may be an important social determinant of racial birth disparities.

Predictors of the Timing of Natural Menopause in the Multiethnic Cohort Study

Henderson, K. D., Bernstein, L., Henderson, B., Kolonel, L., Pike, M. C. — 2008-03-21

The timing of natural menopause has implications for several health endpoints; in particular, it is a risk factor for breast cancer. The authors investigated factors influencing the timing of natural menopause among 95,704 women with a mean age of 59.7 years (10th–90th percentile range, 47.0–71.0) in five racial/ethnic groups in the Multiethnic Cohort Study, including non-Latina Whites, Japanese Americans, African Americans, Native Hawai'ians, and Latinas. The authors investigated whether race/ethnicity and several lifestyle and reproductive characteristics were associated with the timing of natural menopause. Race/ethnicity was a significant independent predictor of the timing of natural menopause. Other factors, including smoking, age at menarche, parity, and body mass index, did not significantly alter the race/ethnicity-specific hazard ratios. Relative to non-Latina Whites, natural menopause occurred earlier among Latinas (US-born Latinas: hazard ratio (HR) = 1.10, 95% confidence interval (CI): 1.07, 1.14; non-US-born Latinas: HR = 1.25, 95% CI: 1.21, 1.30) and later among Japanese Americans (HR = 0.93, 95% CI: 0.90, 0.95). These results support the hypothesis that the timing of natural menopause is driven by a combination of genetic, reproductive, and lifestyle factors.

Macrosocial Determinants of Population Health: Edited by Sandro Galea

Oakes, J. M. — 2008-03-20